The overall objective of this proposal is to study the alterations of hepatic glucose metabolism in endotoxic shock and to delineate the mechanisms responsible for them. The investigation involves (1) the key regulatory enzymes in glycoloysis, gluconeogenesis, glycogen turnover, and the TCA cycle; (2) adenylate cyclase and phosphodiesterase system; (3) membrane marker enzyme systems, etc. One the metabolic alterations have been identified and the mechanisms responsible for them are delineated. Attempts will be made to prevent the onset or to delay the progression of cellular deterioration by pharmacological or metabolic interventions.